Potentially Prognostic miRNAs in HPV-Associated Oropharyngeal Carcinoma
Potentially Prognostic miRNAs in HPV-Associated Oropharyngeal Carcinoma
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DOI：
10.1158/1078-0432.ccr-12-3572
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发表时间：
2013-04-15
影响因子：
11.5
通讯作者：
Liu, Fei-Fei
中科院分区：
文献类型：
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作者：
Hui, Angela B. Y.;Lin, Alice;Liu, Fei-Fei
目的：miRNAs的失调与几乎所有的人类恶性肿瘤有关。人乳头瘤病毒（HPV）相关的口咽癌（OPC）与HPV阴性的OPC相比，具有明显更有利的结果;然而，其潜在的机制尚未得到很好的理解。因此，本研究的目的是确定miRNA表达是否作为HPV状态的函数而不同，并评估这些miRNA是否提供超越HPV状态的预后价值。（p16-阳性：56; p16-阴性：32），其中使用定量实时（qRT）-PCR同时测量365种miRNA加上3种内源对照的表达水平。结果：224个miRNAs在80%以上的样本中表达，其中128个（57%）在肿瘤组织和正常组织中差异表达（P < 0.05）。上调的miR-20 b、miR-9和miR-9* 与HPV/p16状态显著相关。三组miRNA与总生存率显著相关，（miR-107，miR-151，miR-492; P = 0.0002），无病生存期（miR-20 b、miR-107、miR-151、miR-182、miR-361; P = 0.0001），与远处转移（miR-151，miR-152，miR-324- 5 p，miR-361，miR 492; P = 0.0087），即使在调整p16状态后仍保持显著性。这些miRNA的相关生物学功能包括免疫监视、治疗抵抗、侵袭和转移。结论：我们已经确定了几种与OPC中HPV状态相关的miRNA;此外，三种候选预后miRNA集似乎与临床结果相关，独立于p16状态。此外，评估将提供生物学的见解，HPV阳性与HPV阴性OPC之间的差异的机制。临床癌症研究; 19（8）; 2154-62。(C)2013年AACR。
Purpose: Deregulation of miRNAs is associated with almost all human malignancies. Human papillomavirus (HPV)-associated oropharyngeal carcinoma (OPC) has a significantly more favorable outcome compared with HPV-negative OPCs; however, the underlying mechanisms are not well understood. Hence, the objectives of this study were to determine whether miRNA expression differed as a function of HPV status and to assess whether such miRNAs provide prognostic value beyond HPV status.Methods: Global miRNA profilings were conducted on 88 formalin-fixed and paraffin-embedded (FFPE) OPC biopsies (p16-positive: 56; p16-negative: 32), wherein the expression levels of 365 miRNAs plus 3 endogenous controls were simultaneously measured using quantitative real-time (qRT)-PCR. Seven FFPE specimens of histologically normal tonsils were used as controls.Results: Overall, 224 miRNAs were expressed in more than 80% of the investigated samples, with 128 (57%) being significantly differentially expressed between tumor versus normal tissues (P < 0.05). Upregulated miR-20b, miR-9, and miR-9* were significantly associated with HPV/p16-status. Three miRNA sets were significantly associated with overall survival (miR-107, miR-151, miR-492; P = 0.0002), disease-free survival (miR-20b, miR-107, miR-151, miR-182, miR-361; P = 0.0001), and distant metastasis (miR-151, miR-152, miR-324-5p, miR-361, miR492; P = 0.0087), which retained significance even after adjusting for p16 status. The associated biologic functions of these miRNAs include immune surveillance, treatment resistance, invasion, and metastasis.Conclusion: We have identified several miRNAs, which associate with HPV status in OPC; furthermore, three candidate prognostic sets of miRNAs seem to correlate with clinical outcome, independent of p16 status. Furthermore, evaluations will offer biologic insights into the mechanisms underlying the differences between HPV-positive versus HPV-negative OPC. Clin Cancer Res; 19(8); 2154-62. (C) 2013 AACR.